1,4-Dioxane → HCID 89407718, compound

HRID 1524398Notes

Reaction equation

HRID 1524398 reaction equation
Br[C:2]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[CH3:13][N:14]1[C:18](B2OC(C)(C)C(C)(C)O2)=[CH:17][CH:16]=[N:15]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>CO.O>[CH3:13][N:14]1[C:18]([C:2]2[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:3]=2[NH2:4])=[CH:17][CH:16]=[N:15]1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 938992-Bromo-4-trifluoromethylanilineHCID 49129081-methyl-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 89407718HCID 89407718, compoundYield 13.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A round-bottom flask was charged with 2-bromo-4-(trifluoromethyl)aniline (4.115 g, 17.14 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (4.64 g, 22.29 mmol), potassium phosphate (10.92 g, 51.4 mmol), and Pd(AmPhos)2Cl2 (0.607 g, 0.857 mmol). Dioxane (30 mL) and water (10 mL) were added to give a thick suspension. The flask was fitted with a reflux condenser and placed in a 90° C. oil bath for 4 h. The mixture was removed from the heat, then diluted with water and extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The residue was partially purified twice by chromatography on silica gel, first with 25 to 75% EtOAc/Heptane, then with 20 to 70% EtOAc/Heptane. The partially purified material thus obtained was dissolved in methanol and loaded onto a 10 g SCX-2 ion exchange column. The column was eluted with methanol, then with 2N ammonia in methanol. The basic fractions were combined and concentrated to give 2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethyl)aniline (0.5526 g, 2.291 mmol, 13.36% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ=7.52 (d, J=1.9 Hz, 1 H), 7.43 (ddd, J=0.5, 2.3, 8.6 Hz, 1 H), 7.26 (d, J=1.9 Hz, 1 H), 6.88 (d, J=8.5 Hz, 1 H), 6.32 (d, J=1.9 Hz, 1 H), 5.62 (s, 2 H), 3.64 (s, 3 H). m/z (ESI) 242.2 (M+H)+.

Workup

  1. customto give a thick suspension
  2. customThe flask was fitted with a reflux condenser
  3. customplaced in a 90° C.
  4. customfor 4 h
  5. customThe mixture was removed from the heat
  6. additiondiluted with water
  7. extractionextracted with EtOAc (3×)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was partially purified twice by chromatography on silica gel, first with 25 to 75% EtOAc/Heptane
  12. customThe partially purified material thus obtained
  13. washThe column was eluted with methanol
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-edf580ced22c4f38a5f37064d71648b3
Source dataset
uspto-grants-2015_07
Patent number
US09079902B2

Reaction notes

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